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Zhong Jie Fu, Suk-Yee Li, Norbert Kociok, David Wong, Sookja K. Chung, Amy C. Y. Lo; Aldose Reductase Deficiency Reduced Vascular Changes in Neonatal Mouse Retina in Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(9):5698-5712. doi: https://doi.org/10.1167/iovs.12-10122.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal neovascularization is the major pathologic process in many ocular diseases and is associated with oxidative stress. Deficiency of aldose reductase (AR), the first enzyme in the polyol pathway for glucose metabolism, has been shown to reduce oxidative stress and blood vessel leakage. The present study aimed to investigate the effect of AR deficiency on retinal neovascularization in a murine oxygen-induced retinopathy (OIR) model.
Seven-day-old wild-type (WT) and AR-deficient (AR−/−) mice were exposed to 75% oxygen for 5 days and then returned to room air. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. Immunohistochemistry for AR, nitrotyrosine (NT), poly(ADP-ribose) (PAR), glial fibrillary acidic protein (GFAP), and Iba-1, as well as Western blots for vascular endothelial growth factor (VEGF), phospho-Erk (p-Erk), phospho-Akt (p-Akt), and phospho-IκB (p-IκB) were performed.
Compared with WT OIR retinae, AR−/− OIR retinae displayed significantly smaller central retinal vaso-obliterated area, less neovascularization, and reduced blood vessel leakage. Significantly reduced oxidative stress and glial responses were also observed in AR−/− OIR retinae. Moreover, reduced microglial response in the avascular area but increased microglial responses in the neovascular area were found with AR deficiency. Furthermore, expression levels of VEGF, p-Erk, p-Akt, and p-IκB were significantly reduced in AR−/− OIR retinae.
Our observations indicated that AR deficiency reduced retinal vascular changes in the mouse model of OIR, indicating that AR can be a potential therapeutic target in ischemia-induced retinopathy.
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